Our previous studies have suggested that mitochondrial dysfunction causes oxidative DNA damage and contributes to tumorigenesis. A major contributing factor is ambient oxygen which is the essential substrate for reactive oxygen species generation that can cause biological damage. Environmental and genetic methods will be used to modulate redox homeostasis and to determine their effect on energy metabolism, tumorigenesis, and cardiovascular function. We are also examining the adaptive mechanisms by which cells can survive under oxidative or other cellular stress conditions. One concept that has emerged is the possibility of protecting the mitochondrial genome for prevention of doxorubicin cardiomyopathy.